triapine + fludarabine

Triapine (3-AP) is a small molecule ribonucleotide reductase (RNR) inhibitor that specifically targets the M2 subunit of the enzyme. By inhibiting RNR, Triapine depletes intracellular deoxyribonucleotide pools, particularly dATP, which are essential for DNA synthesis and repair. This depletion can sensitize cancer cells to the effects of other antineoplastic agents. In clinical trials conducted by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Triapine was administered sequentially with fludarabine, a purine analog antimetabolite. Fludarabine is phosphorylated to its active form, F-ara-ATP, which inhibits DNA polymerase and ribonucleotide reductase, and incorporates into DNA to induce apoptosis. The sequential combination of Triapine followed by fludarabine is designed to exploit biochemical modulation, where RNR inhibition by Triapine increases the cellular uptake and activation of fludarabine, thereby enhancing its cytotoxic activity against various hematologic malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).

Brand names

Fludara

Other names

3-aminopyridine-2-carboxaldehyde thiosemicarbazonefludarabine phosphate